Adult somatic stem cells are thought to be responsible for the continued self renewal of the epidermis. Although hair follicle stem cells in the bulge have been well characterized, our understanding of stem cells in the interfollicular epidermis remains poor. We have discovered unique cells within human and mouse postnatal skin which co-express the stem cell marker CD133 and basal marker alpha6 integrin. Our preliminary studies indicate that these cells exist in discrete patches within interfollicular basal epithelium, express stem cell genes such as nanog and achaete scute-like 3 and may generate new hair follicles in in vivo reconstitution ("patch") assays. We postulate that these cells are true multipotent interfollicular stem cells, capable of self renewal and the regeneration of skin components, specifically epidermis and hair follicles. We will use human and mouse models to test this hypothesis. The discovery of an interfollicular stem cell population with multipotent capability would have high impact on skin biology, challenging current models of skin and HF regeneration, and provide a powerful new tool for therapeutic treatment of chronic wounds and alopecia. PUBLIC HEALTH RELEVANCE: We will study stem cells in the outer portion of the skin called the epidermis. The goal is to better understand the cells responsible for the constant production of this layer and its remarkable response to wounding. Ultimately, this research may impact on developing new treatments for skin problems such as chronic wounds, burns, alopecia and skin aging.